Retinoic acid leads to cytoskeletal rearrangement through AMPK-Rac1 and stimulates glucose uptake through AMPK-p38 MAPK in skeletal muscle cells.
Retinoic acid (RA) is one of the major components of vitamin A. In the present study, we found that retinoic acid activated AMP-activated protein kinase (AMPK). RA induced Rac1-GTP formation and phosphorylation of its downstream target, p21-activated kinase (PAK), whereas the inhibition of AMPK blocked RA-induced Rac1 activation. Moreover, cofilin, an actin polymerization regulator, was activated when incubated with RA. We then showed that inhibition of AMPK by compound C, a selective inhibitor of AMPK, or small interfering RNA of AMPK alpha1 blocked RA-induced cofilin phosphorylation. Additionally, we found that retinoic acid-stimulated glucose uptake in differentiated C2C12 myoblast cells and activated p38 mitogen-activated protein kinase (MAPK). Finally, the inhibition of AMPK and p38 MAPK blocked retinoic acid-induced glucose uptake. In summary, our results suggest that retinoic acid may have cytoskeletal roles in skeletal muscle cells via stimulation of the AMPK-Rac1-PAK-cofillin pathway and may also have beneficial roles in glucose metabolism via stimulation of the AMPK-p38 MAPK pathway.
Lee
Yun Mi
YM
Department of Anatomy, Korea University College of Medicine, Seoul 136-1705, Korea.
Lee
Jung Ok
JO
Jung
Jin-Hee
JH
Kim
Ji Hae
JH
Park
Sun-Hwa
SH
Park
Ji Man
JM
Kim
Eung-Kyun
EK
Suh
Pann-Ghill
PG
Kim
Hyeon Soo
HS
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D051338:Cofilin 1 / Q000737:chemistry; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein
D051338:Cofilin 1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009479:Neuropeptides; D034741:RNA, Small Interfering; C484602:Rac1 protein, mouse; D014212:Tretinoin; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D005947:Glucose